A number of quinolone compounds have been developed and proven successful in commerce, attributed to their potent and broad spectrum of antibacterial activities. Included among such quinolone compounds are Norfloxacine, Enoxacine, Ofloxacine, Ciprofloxacine and the like.
In recent years, extensive investigation has been made to develop a novel structure of pyridone carboxylic acid derivatives which have more potent and broad antibacterial activities. Most of such investigation has been into the development of new substituents at 7-position of the quinolone nucleus. As prior art references which disclose such derivatives, U.S. Pat. No. 4,988,709, European Patent 0413 455 and Japanese Unexamined Patent Publication 89-56673 may be mentioned.
We have found another class of novel compounds of formula(I) which is claimed in pending U.S. Ser. No. 08/160821 filed Dec. 3, 1993. As the compounds of formula (I) as represented below were in vitro evaluated about their efficacy, it was found that these compounds, especially 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-([1.alpha.,5.alpha.,6.beta.]6-a mino-1-methyl-3-azabicyclo[3.2.0]heptan-3-yl)-1,8-naphtyridine-3-carboxylic acid (hereinafter "compound A") exhibit superior antibacterial activities to Lomefiroxacin and Ofiofioxacine which are utilized for-combating gram-negative and gram-positive bacteria and that these compounds including compound A has 2 to 16 times as much antibacterial activity as Ciprofloxacin, especially against gram-positive bacteria. Moreover, the compounds of formula(I) as represented above, especially compound A, show better bioavailability and half-life than drugs of quinolone compounds which either are commercially available or still in development.
We have conducted much investigation in developing advantageous ways for orally administrating the compounds of formula(I). Therefore, it is the object of the present invention to provide the pharmaceutical formulations of the formula(I) compounds to be orally administrated.